Triptolide is a diterpenoid triepoxide extracted from the root of Tripterygium wilfordii with immunosuppressive, anti-inflammatory, antiproliferative and antitumour effects. Triptolide is a NF-κB activation inhibitor^{[1][2][3][4][5][6]}.

Triptolide induces apoptosis in cultured and primary Chronic Lymphocytic Leukemia (CLL) B-cells. Treatment of CD19⁺ B cells with Triptolide, induces a dose-dependent increase in apoptosis in cultured and primary CLL cells. Triptolide is selectively toxic to both high risk (n=5) and low risk CLL (n=12) B cells (10 to 50 nM range) while largely sparing normal B-cells (n=5). Consistent with the inhibition of heat-shock induced HSP transcription, treatment with Triptolide attenuates heat-shock induced expression of HSPs^[1]. Triptolide is a natural product derived from the Chinese plant Tripterygium wilfordii, is reported to exhibit antitumor effects in a broad range of cancers. Triptolide inhibits MDM2 expression in a dose-dependent manner, even at low concentrations spanning 20-100 nM in acute lymphoblastic leukemia (ALL) cells. Triptolide exhibits strongly cytotoxic activity in all 8 cell lines having native MDM2 overexpression, with IC₅₀ values range from 47 to 73 nM. Triptolide exhibits much less cytotoxic effect on EU-4 cells that express very low level of MDM2, while it effectively kill these cells when MDM2 is stably transfected (IC₅₀ values: 725 nM vs. 88 nM)^[2]. Differentiated PC12 cells are incubated with different concentrations of Triptolide (0.01, 0.1, and 1 nM) in the presence of 10 μM Aβ_25-35 for 24 hours and MTT assay is used to detect the effect of Triptolide. The results show that Aβ_25-35 can decrease the cell viability and when treated with Triptolide the viability of differentiated PC12 cells is significantly increased. The results indicate that Triptolide can alleviate cellular damage caused by Aβ_25-35, which means that Triptolide has a neuroprotective effect^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

The Triptolide (TP) plasma concentrations are declined rapidly in mice after receive an intravenous dose. After 2h of injection, the Triptolide concentrations are dropped below the lower limit of quantification for all three groups. A comparison of the parameters is made between the control and the treated groups to assess the effect of P-gp inhibition on the Triptolide exposure and elimination. Treatment with the mdr1a-siRNA can significantly enhance the Triptolide plasma exposure, with the C_max increases from 413±74 to 510±94 ng/mL (P<0.05) and the AUC from 103.5±9.6 to 154.3±30.2 ng•h/mL (P<0.05). In the concomitant group with Tariquidar, the significantly increased AUC is also noted, from 103.5±9.6 of the control to 145.9±24.6 ng•h/mL of the Triptolide+Tariquidar group (P<0.05). Accordingly, the total body clearance of Triptolide in mice is remarkably decreased, from 9564±1024.2 mL/min/kg of the control to 6576.4±1438.5 (P<0.05) and 5755.4±1200.1 mL/min/kg (P<0.05) for Triptolide+Tariquidar and Triptolide+mdr1a-siRNA groups, respectively^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

360.40

C₂₀H₂₄O₆

38748-32-2

雷公藤甲素；雷藤素甲；雷公藤内酯醇；雷公藤多甙

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

DMSO : ≥ 33 mg/mL (91.56 mM)

H₂O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)

* “≥” means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 1.17 mg/mL (3.25 mM); Clear solution

  此方案可获得 ≥ 1.17 mg/mL (3.25 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 11.7 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 1.17 mg/mL (3.25 mM); Clear solution

  此方案可获得 ≥ 1.17 mg/mL (3.25 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 11.7 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 1.17 mg/mL (3.25 mM); Clear solution

  此方案可获得 ≥ 1.17 mg/mL (3.25 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 11.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Ganguly S, et al. Targeting HSF1 disrupts HSP90 chaperone function in chronic lymphocytic leukemia. Oncotarget. 2015 Oct 13;6(31):31767-79.

  [2]. Huang M, et al. Triptolide inhibits MDM2 and induces apoptosis in acute lymphoblastic leukemia cells through a p53-independent pathway. Mol Cancer Ther. 2013 Feb;12(2):184-94.

  [3]. Xu P, et al. Triptolide Inhibited Cytotoxicity of Differentiated PC12 Cells Induced by Amyloid-Beta25-35 via the Autophagy Pathway. PLoS One. 2015 Nov 10;10(11):e0142719.

  [4]. Kong LL, et al. Inhibition of P-glycoprotein Gene Expression and Function Enhances Triptolide-induced Hepatotoxicity in Mice. Sci Rep. 2015 Jul 2;5:11747.

  [5]. Zhang W, et al. Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism. Int J Mol Sci. 2016 Dec 19;17(12). pii: E2139.

  [6]. Cai J, et al. Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ. J Exp Clin Cancer Res. 2021;40(1):190. Published 2021 Jun 9.

The viability of differentiated PC12 cells treated with different concentrations of Triptolide. After differentiated PC12 cells are cultured on 96-well plates with RPMI 1640 medium for stabilization, differentiated PC12 cells are incubated with different concentrations of Triptolide (0.01, 0.1, and 1 nM) for 24 hours. The concentrations in this study are chosen. Then cell viability is determined by the MTT assay. Each condition and experiment is repeated three times^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[4]
Male BALB/C mice (weight, 18-22 g) are used. For Triptolide (TP) plasma kinetic study and toxicological evaluation, mice are divided into four groups (n=5 each) to collect blood and tissue samples: (1) normal+saline group; (2) 1.0 mg/kg Triptolide+15 nmol negative control (NC) siRNA-siRNA group; (3) 1.0 mg/kg Triptolide+15 nmol mdr1a-siRNA group; (4) 1.0 mg/kg Triptolide+10 mg/kg Tariquidar group. In order to avoid the complication caused by drug absorption or possible intestinal first-pass effect, Triptolide and the inhibitor are intravenously administrated to mice. The siRNA group is intravenously injected with NC-siRNA or mdr1a-siRNA 2 days before Triptolide dose. For Triptolide+Tariquidar group, the mice are received an intravenous Tariquidar dose 20 min prior to the Triptolide injection. Blood samples are collected at 2, 5, 10, 15, 30, 60 and 120 min after Triptolide dosing. To assess the liver exposure of Triptolide, liver tissue samples are collected from another set of mice at 5, 30, 60 and 120 min after dosing. Three Triptolide groups are design for this experiment, including Triptolide+NC-siRNA group, Triptolide+mdr1a-siRNA group and Triptolide+Tariquidar group. The liver tissue samples are weighed and then homogenized in 10 volume (w:v) of ice-cold saline. The concentrations of Triptolide in plasma and liver tissue are measured by a validated LC-MS/MS method.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Ganguly S, et al. Targeting HSF1 disrupts HSP90 chaperone function in chronic lymphocytic leukemia. Oncotarget. 2015 Oct 13;6(31):31767-79.

  [2]. Huang M, et al. Triptolide inhibits MDM2 and induces apoptosis in acute lymphoblastic leukemia cells through a p53-independent pathway. Mol Cancer Ther. 2013 Feb;12(2):184-94.

  [3]. Xu P, et al. Triptolide Inhibited Cytotoxicity of Differentiated PC12 Cells Induced by Amyloid-Beta25-35 via the Autophagy Pathway. PLoS One. 2015 Nov 10;10(11):e0142719.

  [4]. Kong LL, et al. Inhibition of P-glycoprotein Gene Expression and Function Enhances Triptolide-induced Hepatotoxicity in Mice. Sci Rep. 2015 Jul 2;5:11747.

  [5]. Zhang W, et al. Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism. Int J Mol Sci. 2016 Dec 19;17(12). pii: E2139.

  [6]. Cai J, et al. Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ. J Exp Clin Cancer Res. 2021;40(1):190. Published 2021 Jun 9.